G.P.77 Deletions in the dystrophin gene predict loss of ambulation before 10 years of age in boys with Duchenne muscular dystrophy

Abstract

There is considerable variation in the rate of disease progression and response to steroid therapy in males with Duchenne muscular dystrophy (DMD). Genetic influences may explain at least part of this heterogeneity. This retrospective case series explored the relationship between dystrophin gene mutations (DMD) and age at loss of ambulation (LOA). Medical histories (n=144) were examined from two Australian neuromuscular clinics. Data were collected on clinical characteristics including DMD mutation type and location, age at LOA, anthropometry, lung function and steroid use. The relationship between age at LOA and genetic and clinical characteristics including age at chart review, duration of steroid treatment, and BMI z-score was explored via multiple regression analysis. Significant independent variables were also entered in a logistic regression to predict LOA <10years of age. The mean (±SD) age of the cohort was 11.9±4.0years, and 51% of boys had lost the ability to walk independently. Mutation type and duration of steroid treatment were significant independent predictors of LOA <10years in a logistic model explaining 31.2% of the variance in age of LOA. Boys with deletions in the dystrophin gene were six times more likely to stop walking before age 10 compared to boys with duplications, point or unknown mutations. This was reflected in the mean age at LOA in boys with deletions versus other mutations (9.30±1.60 vs 10.97±2.03years, respectively, p<0.0005). A longer duration of steroid therapy was associated with a reduction in risk of LOA <10years. BMI had no relationship with age at LOA. Whilst the negative effects of steroid treatment such as weight gain and decreased bone health need to be considered, early introduction of steroids may provide some functional benefits, especially to boys with a documented deletion in DMD gene.